Evaluation of Brain Lesions in HIV-infected Patients for Diagnosis of Primary Central Nervous System Lymphoma
| Status: | Completed |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | September 2005 |
| End Date: | April 2009 |
The Evaluation of Focal Contrast-Enhancing Brain Lesions in HIV-Infected Patients
This study will evaluate the usefulness of two tests in quickly distinguishing whether a
patient with HIV infection and focal brain lesions (an injury in a specific area of the
brain) has a rare type of cancer called primary central nervous system lymphoma (PCNSL), or
a parasitic infection called toxoplasmic encephalitis.
Toxoplasmic encephalitis is caused by a parasite and can be treated with antibiotics. PCNSL
(lymphoma of the brain or spinal cord) must be definitively diagnosed with a brain biopsy
(removal of a small piece of brain tissue), and the treatment is radiation therapy and
chemotherapy.
The tests under study for diagnosing PCNSL or toxoplasmic encephalitis are measurement of
Epstein Barr virus (EBV) DNA in cerebrospinal fluid (CSF) and FDG-PET scan of the brain. EBV
is often found in the CSF of people with PCNSL. The study also will compare the accuracy of
two imaging techniques-TI-SPECT and FDG-PET-in distinguishing between toxoplasmosis and
PCNSL.
Patients 18 years of age and older who have HIV infection and at least one focal brain
lesion without a prior history of PCNSL or toxoplasmic encephalitis may be eligible for this
study. Each candidate is screened with a medical history, physical examination, blood and
urine tests and MRI scans of the brain.
Upon entering the study, all participants take medication to treat toxoplasmic encephalitis.
They undergo lumbar puncture (spinal tap) to obtain CSF for analysis, an FDG-PET scan, and a
201TI-SPECT scan. For the PET scan, a radioactive substance is injected into an arm,
followed by scanning in a doughnut-shaped machine similar to a CT scanner. SPECT is similar
to PET but uses a different radioactive tracer, and the patient lies on a table while the
SPECT camera rotates around the patient's head. Patients whose test results indicate a low
risk for lymphoma continue antibiotic therapy for toxoplasmosis. They have repeat MRI scans
around 4, 7, and 14 days after starting the drug to monitor the response to therapy.
Antiretroviral therapy is initiated in patients who are not already on such a regimen.
Patients whose test results indicate a high risk for PCNSL have a CT scan to look for
evidence of lymphoma elsewhere in the body and are referred for consultation with a
neurosurgeon to discuss undergoing a brain biopsy. The brain biopsy is done in the operating
room under general anesthesia. A small cut is made in the scalp and a small opening is made
in the skull over the area of the brain to be biopsied. A needle is placed in the opening in
the skull and, guided by CT or MRI, moved to the abnormal area of the brain, where a small
piece of tissue is removed for study under a microscope.
Patients found to have toxoplasmosis are discharged from the hospital to the care of their
primary care physician after they are getting better and are tolerating all their
medications. They return to NIH for follow-up visits about 4 weeks, and 6 months after
discharge.
Patients found to have lymphoma are referred to the National Cancer Institute for screening
for enrollment in a treatment protocol. Patients who are not eligible for a treatment
protocol are referred back to their primary care physician or for another NIH treatment
protocol, if one is available. Patients with lymphoma are seen at the NIAID outpatient
clinic for follow-up visits and laboratory examinations every 3 months for 2 years.
patient with HIV infection and focal brain lesions (an injury in a specific area of the
brain) has a rare type of cancer called primary central nervous system lymphoma (PCNSL), or
a parasitic infection called toxoplasmic encephalitis.
Toxoplasmic encephalitis is caused by a parasite and can be treated with antibiotics. PCNSL
(lymphoma of the brain or spinal cord) must be definitively diagnosed with a brain biopsy
(removal of a small piece of brain tissue), and the treatment is radiation therapy and
chemotherapy.
The tests under study for diagnosing PCNSL or toxoplasmic encephalitis are measurement of
Epstein Barr virus (EBV) DNA in cerebrospinal fluid (CSF) and FDG-PET scan of the brain. EBV
is often found in the CSF of people with PCNSL. The study also will compare the accuracy of
two imaging techniques-TI-SPECT and FDG-PET-in distinguishing between toxoplasmosis and
PCNSL.
Patients 18 years of age and older who have HIV infection and at least one focal brain
lesion without a prior history of PCNSL or toxoplasmic encephalitis may be eligible for this
study. Each candidate is screened with a medical history, physical examination, blood and
urine tests and MRI scans of the brain.
Upon entering the study, all participants take medication to treat toxoplasmic encephalitis.
They undergo lumbar puncture (spinal tap) to obtain CSF for analysis, an FDG-PET scan, and a
201TI-SPECT scan. For the PET scan, a radioactive substance is injected into an arm,
followed by scanning in a doughnut-shaped machine similar to a CT scanner. SPECT is similar
to PET but uses a different radioactive tracer, and the patient lies on a table while the
SPECT camera rotates around the patient's head. Patients whose test results indicate a low
risk for lymphoma continue antibiotic therapy for toxoplasmosis. They have repeat MRI scans
around 4, 7, and 14 days after starting the drug to monitor the response to therapy.
Antiretroviral therapy is initiated in patients who are not already on such a regimen.
Patients whose test results indicate a high risk for PCNSL have a CT scan to look for
evidence of lymphoma elsewhere in the body and are referred for consultation with a
neurosurgeon to discuss undergoing a brain biopsy. The brain biopsy is done in the operating
room under general anesthesia. A small cut is made in the scalp and a small opening is made
in the skull over the area of the brain to be biopsied. A needle is placed in the opening in
the skull and, guided by CT or MRI, moved to the abnormal area of the brain, where a small
piece of tissue is removed for study under a microscope.
Patients found to have toxoplasmosis are discharged from the hospital to the care of their
primary care physician after they are getting better and are tolerating all their
medications. They return to NIH for follow-up visits about 4 weeks, and 6 months after
discharge.
Patients found to have lymphoma are referred to the National Cancer Institute for screening
for enrollment in a treatment protocol. Patients who are not eligible for a treatment
protocol are referred back to their primary care physician or for another NIH treatment
protocol, if one is available. Patients with lymphoma are seen at the NIAID outpatient
clinic for follow-up visits and laboratory examinations every 3 months for 2 years.
Epstein Barr Virus (EBV)-associated primary central nervous system lymphoma (PCNSL) remains
a major problem among AIDS patients. The clinical presentation is often clinically
indistinguishable from toxoplasmic encephalitis. The method of choice for establishing the
definitive diagnosis is brain biopsy. This procedure can be associated with a significant
morbidity and mortality, and therefore less invasive means of diagnosing cerebral mass
lesions have been studied.
Currently, an accepted standard of care for HIV-infected patients that present with signs
and symptoms of focal brain lesions is to empirically treat for toxoplasmic encephalitis.
Brain biopsy is often deferred until there is demonstration of lack of clinical response or
progression on empiric therapy. As a result, treatment initiation is frequently delayed.
During this time it is not unusual for further clinical deterioration to occur before
appropriate therapies can be initiated. Frequently, the alternative approaches then become a
question of appropriate palliation rather than curative intent therapy.
Less invasive diagnostic tests to assist in the diagnosis have been investigated. Based on
the finding that essentially 100% of HIV-related PCNSL are EBV-associated, the detection of
EBV DNA by PCR amplification in the cerebrospinal fluid (CSF) has demonstrated clinical
usefulness in the diagnosis, as has the use of neuroradiologic imaging to detect the
malignancy. Prior studies have demonstrated that the use of a combination of
neuroradiologic, immunologic, and clinical variables in the workup of focal brain lesions in
HIV-infected patients to be quite accurate in identifying patients in need of brain biopsy,
but a diagnostic algorithm that incorporates the combination of the most sensitive and
specific tests in a timely manner has not yet been explored.
This study seeks to evaluate an algorithm for the workup of HIV infected patients with focal
brain lesions so as to expedite the diagnosis and subsequent treatment of PCNSL. The goals
of the study are to 1) determine the specificity, sensitivity, and positive predictive value
of a diagnostic algorithm that entails the use of the combination of EBV detection in the
CSF and FDG-PET scanning to diagnose PCNSL; 2) evaluate the time to response to
anti-toxoplasmic encephalitis therapy, and 3) evaluate the sensitivities and specificities
of FDG-PET and (201)Tl-SPECT scanning in identifying PCNSL. Up to one hundred HIV-infected
patients with history of at least one focal brain lesion will be screened for enrollment.
All patients will be treated empirically for toxoplasmic encephalitis until an alternative
diagnosis is confirmed. All enrolled patients will be treated concurrently with
antiretroviral therapy. Patients identified to have PCNSL will be referred to the NCI
Treatment of PCNSL Protocol for further treatment if the study is open for enrollment.
a major problem among AIDS patients. The clinical presentation is often clinically
indistinguishable from toxoplasmic encephalitis. The method of choice for establishing the
definitive diagnosis is brain biopsy. This procedure can be associated with a significant
morbidity and mortality, and therefore less invasive means of diagnosing cerebral mass
lesions have been studied.
Currently, an accepted standard of care for HIV-infected patients that present with signs
and symptoms of focal brain lesions is to empirically treat for toxoplasmic encephalitis.
Brain biopsy is often deferred until there is demonstration of lack of clinical response or
progression on empiric therapy. As a result, treatment initiation is frequently delayed.
During this time it is not unusual for further clinical deterioration to occur before
appropriate therapies can be initiated. Frequently, the alternative approaches then become a
question of appropriate palliation rather than curative intent therapy.
Less invasive diagnostic tests to assist in the diagnosis have been investigated. Based on
the finding that essentially 100% of HIV-related PCNSL are EBV-associated, the detection of
EBV DNA by PCR amplification in the cerebrospinal fluid (CSF) has demonstrated clinical
usefulness in the diagnosis, as has the use of neuroradiologic imaging to detect the
malignancy. Prior studies have demonstrated that the use of a combination of
neuroradiologic, immunologic, and clinical variables in the workup of focal brain lesions in
HIV-infected patients to be quite accurate in identifying patients in need of brain biopsy,
but a diagnostic algorithm that incorporates the combination of the most sensitive and
specific tests in a timely manner has not yet been explored.
This study seeks to evaluate an algorithm for the workup of HIV infected patients with focal
brain lesions so as to expedite the diagnosis and subsequent treatment of PCNSL. The goals
of the study are to 1) determine the specificity, sensitivity, and positive predictive value
of a diagnostic algorithm that entails the use of the combination of EBV detection in the
CSF and FDG-PET scanning to diagnose PCNSL; 2) evaluate the time to response to
anti-toxoplasmic encephalitis therapy, and 3) evaluate the sensitivities and specificities
of FDG-PET and (201)Tl-SPECT scanning in identifying PCNSL. Up to one hundred HIV-infected
patients with history of at least one focal brain lesion will be screened for enrollment.
All patients will be treated empirically for toxoplasmic encephalitis until an alternative
diagnosis is confirmed. All enrolled patients will be treated concurrently with
antiretroviral therapy. Patients identified to have PCNSL will be referred to the NCI
Treatment of PCNSL Protocol for further treatment if the study is open for enrollment.
- INCLUSION CRITERIA:
Adult (18 years old or older) HIV-infected patient
HIV infected by OraQuick rapid test using saliva, venipuncture whole blood, or fingerstick
whole blood; or by reactive ELISA and Western Blot as determined by an outside
CLIA-approved laboratory facility or by NIH Clinical Pathology Laboratory or
SAIC-Frederick Inc Monitoring Laboratory. HIV infection as determined by an outside
CLIA-approved laboratory facility will be verified by a standard HIV-1 ELISA with Western
Blot confirmation prior to brain biopsy.
Evidence of contrast-enhancing focal brain lesion(s) as seen on MRI or CT
Willingness to give informed consent and provided by Durable Power of Attorney. In the
event that no Durable Power of Attorney has been designated and the patient is unable to
do so, the NIH Ethics Committee will be consulted. All patients must designate a Durable
Power of Attorney in order to participate in the study.
Willingness to undergo the procedures involved in the diagnostic evaluation: lumbar
puncture, FDG-PET scan, 201Tl-SPECT scan, and brain biopsy.
Permit the storage of blood, CSF, and tissue samples for future research use
Willingness to undergo HLA testing
EXCLUSION CRITERIA:
Previous PCNSL
History of prior malignancy other than PCNSL unless in remission for 1 year or longer;
non-melanoma skin cancer and Kaposi's sarcoma excepted
History of previous diagnosis of toxoplasmic encephalitis or other CNS infection causing
focal contrast-enhancing brain lesions
Pregnancy or currently breast feeding
Have any other condition that the research team considers a contraindication to
participating in the study, e.g. severe cardiac, renal, or pulmonary dysfunction.
Weight greater than 400 lb for PET and 500 lb for SPECT (limit of the gantry).
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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